The bacterium Streptococcus pneumoniae is a frequent cause of pneumonia, bacteremia, meningitis, and otitis media in adults and children. Immunological host defenses against S. penumoniae include: 1) antibodies to type-specific penumococcal capsular polysaccharides (PPS); 2) antibodies to phosphocholine (PC) determinants of the bacterial cell wall; 3) C-reactive protein (CRP), an acute phase reactant which binds to PC determinants; 4) complement; and 5) reticuloendothelial cells, including those of the liver and spleen. In this study I propose to: 1) Measure anti-PPS and anti-PC antibodies and CRP by enzyme immunoassays in patients immunized with PPS vaccine or following S. pneumoniae infections to determine their clinical relevance to protection; 2) Develop marmoset and later human monoclonal antibodies to PPS and PC with hybridoma technology to use in opsonization, clearance, and protection studies; 3) Determine the relative effectiveness and interactions of anti-PPS and anti-PC antibodies and CRP as opsonins of S. pneumoniae in vitro by radiolabelled bacterial uptake and chemiluminescence assays; 4) Use the marmoset as a primate model to study the clearance and organ sequestration of S. pneumoniae opsonized by anto-PPS and anti-PC antibodies and CRP; and 5) Investigate the relative effectiveness of monoclonal anti-PPS and anti-PC antibodies, and CRP, in protecting animals from experimental S. pneumoniae bacteremia. Such a study would provide the experimental basis for the eventual treatment of patients with S. pneumoniae infections with specific, protective monoclonal antibodies.